Sugar/sugar alcohol esters

ABSTRACT

The invention disclosed relates to a process for the preparation of sugar and sugar alcohol esters of general formula I (R-COO-)n-R1(I) wherein R is an alkyl group, R1 is derived from a sugar or a polyol moiety and n is 1 to 3, comprising reacting a sugar or a polyol with an acyl moiety, such as a carboxylic acid or ester, in a suitable solvent therefor and in the presence of an enzymatic catalyst capable of catalyzing the formation of ester bonds, and under reduced pressure sufficient to vaporize the solvent and by-product water, and continuously removing the water.

FIELD OF THE INVENTION

This invention relates to a process for the preparation of sugar andsugar alcohol esters.

Fatty acid esters of sugars and sugar alcohols constitute a veryinteresting group of non-ionic surfactants with potentially importantapplications in many industries because of their surface activeproperties due to their composition. This type of amphiphilic moleculehas very good emulsifying, stabilizing or conditioning effects. Inaddition to be the conjugates of renewable feedstocks, inexpensive andreadily available, they are not harmful to the environment because theyare completely biodegradable under aerobic and anaerobic conditions,they are non-toxic, non-skin irritants, odourless and tasteless and theygive normal food products after human and animal digestion. For allthose reasons, they can be used in numerous areas particulary forenhanced oil recovery, in environmental detoxification processes, inpharmaceutical, detergent, cosmetic, food, and agricultural industries.

In spite of the above mentioned advantages, synthesis of esters ofsugars or sugar alcohols is limited. Such products are obtained withdifficulty by standard chemical esterification, because these techniquesinvolve high temperatures which cause coloration of the final productsand dehydration and cyclization in the case of sugar alcohols. Toovercome these problems, esters of sugars or sugar alcohols can beprepared with a biological catalyst under very mild conditions, but theyhave not been used on a large scale in industry because of thedisadvantages associated with the preparation thereof.

DESCRIPTION OF THE PRIOR ART

The synthesis of sugar esters has been reported by Seino et al. inaqueous media between different sugars (sucrose, glucose, fructose,sorbitol) and fatty acids (stearic, oleic, linoleic acids) in J. Amer.Oil Chem. Soc. vol. 61, 1984, page 1761-1765. Also see U.S. Pat. No.4,614,718. However, this technique using the lipase of Candidacylindracea does not give significant quantities and cannot be used forindustrial purposes.

Various authors (Therisod et al., J. Am. Chem. Soc., vol 108, 1986, page5638-5640; Riva et al., J. Am. Chem. Soc., vol 110, 1988, page 584-589;Chopineau et al, Biotechnol. Bioeng., vol. 31, 1988, page 208-214) havemade sugar esters with porcine pancreatic lipase, Chromobacteriumviscosum lipase or subtilisin (Bacillus subtilis protease) in organicsolvents in which both sugars and fatty acids are soluble. The yield isbetter but they use solvents such as pyridine or dimethylformamide, bothvery toxic substances and absolutely non-compatible with industrialpurposes. Furthermore, to increase the rate of the reaction, they usetrichloroethylesters of fatty acids instead of fatty acids, which arealso non-compatible with industrial purposes.

Khaled et al. have done the synthesis of sugar esters with Lipozyme(Mucor miehei lipase) in tertiary alcohols (French Patent no. 2 646 439;Biotechnol. Lett., vol. 13, 1991, page 167-172). These polar alcoholscan solubilize fatty acids, some sugars and sugars alcohols without anyreactivity. Still, for many sugars, solubility is very low (glucose andsaccharose for example).

In order to increase the solubility, it has been proposed to useorganicboronic acids which are known to solubilize sugars in non-polarorganic solvents by forming a carbohydrate-boronate complex byreversible condensation with carbohydrates. In this case, yieldsobtained in closed vials are noticeably increased (Schlottenbeck et al.,Biotechnol. Lett., vol. 15, 1993, page 61-64; Oguntimein et al.,Biotechnol. Lett., vol. 15, 1993, page 175-180; Ikeda et al.,Biotechnol. Bioeng., vol.42, 1993, page 788-791). However, the fact thatesterification is an equilibrium reversible reaction must be kept inmind. Indeed, the presence of the reaction products in the media limitsthe reaction to a maximum that cannot be theoretically exceeded instoppered reactors. Besides, water liberated by the reaction affectsdirectly the activity of the lipase which is known to have its maximumesterase activity within a strict hydration range.

To displace the equilibrium of the reaction, some researchers haveperformed the synthesis under reduced pressure in a solvent-freeprocess. Therefore, the water liberated by the reaction is vaporized andeliminated without inhibiting the esterase activity of the enzyme andthus, favouring synthesis. However, the starting molten materials arenot miscible together, and no reaction appears until substratemiscibility is increased. To overcome this problem, sugar acetals orsugar alkyl glucosides must be used. In addition, obtained products arenot even the desired products since they do not show the desiredproperties. Further chemical transformations must be performed to yieldthe desired compounds (Fregapane et al., Enzyme Microb. Technol., vol.13, 1991, page 796-800; Bjorkling et al., J. Chem. Soc., Chem. Comm.,vol. 14, 1989, page 934-935; Bjorkling et al., Synthesis, vol. 2, 1990,page 112-115; Kirk et al., Biocatalysis, vol. 6, 1992, page 127-134).

The situation can be summarized as follows:

In the literature, three major problems inherent in the reaction aredisplayed:

1: The starting materials (sugar or sugar alcohol and fatty acid) haveopposite polarities.

2: Esterification between a fatty acid and an alcohol is a reversiblereaction leading to limited ester yields.

3: Water generated by the reaction increases significantly the wateractivity of the media, which in turn affects the esterase activity ofthe enzyme (biocatalyst inhibition), if it is not removed.

SUMMARY OF THE INVENTION

The method according to the invention takes care of all three problemspresented above inherent in sugar ester synthesis by carrying out thereaction at once in solvent media and under reduced pressure. Theoriginality of the process involves drying the solvent in a continuousfashion as follows: the pressure is lowered so that the solventcontaining water is allowed to reflux thus vaporizing at the reactiontemperature. Next, it is recondensed and is dried by passing through awater trap (such as molecular sieves for example) before returning tothe reaction media. Since the adsorption agent is not directly in thereaction media, it does not affect at any time the different products ofthe reaction or the biocatalyst during the reaction or their recovery atthe end of the reaction. Furthermore, the adsorption agent is veryeasily recoverable and reusable many times after just simple drying.Lowering the pressure permits to have the solvent refluxing at theoptimum temperature of the biocatalyst.

This process allows the use of a vast number of solvents with a largerange of boiling point, from those having elevated boiling points above100° C. at atmospheric pressure, to those having boiling points below100° C. if the solvent forms an azeotrope with water. The preferredprocess temperature is dictated by the stability of the enzyme used. Forexample, in the case of Candida antarctica type B lipase, it is around50°-70° C. The preferred pressure is the boiling pressure of the solventat the preferred temperature when solvents have boiling point below 100°C. at atmospheric pressure and form an azeotrope with water. In the caseof solvents having boiling points above 100° C. at atmospheric pressure,the pressure is lowered enough to allow boiling of the by-product water(120-300 millibars for 50°-70° C.). This approach contributes to thenovelty of the process.

Thus, the proposed process directly relates to the three problemspresented above:

1: it increases the contact between the two substrates by the use of alarge range of solvents,

2: it eliminates the water generated by the reaction in a continuousfashion without the loss of any solvent which in turn allows theequilibrium to be displaced towards synthesis,

3: it maintains the water activity required by the enzyme given thatthere is no water accumulation in the media.

According to one aspect of the invention, a process for the preparationof a sugar or sugar alcohol ester of general formula I

    (R--COO--).sub.n --R.sup.1                                 (I)

wherein R is an alkyl group which can be saturated or unsaturated,linear or branched and substituted or unsubstituted, n is 1 to 3 and R¹is derived from a sugar or a polyol containing the moiety ##STR1## isprovided, comprising reacting a sugar or a sugar polyol of formula

    R.sup.1 --(OH).sub.n

wherein R¹ and n are as defined above, with an acyl moiety of theformula

    R--CO--X

wherein R is as defined above and X is OH, OR', Cl or OOCR", in which R'and R" are an alkyl chain which can be saturated or unsaturated, linearor branched and substituted or unsubstituted, in an solvent therefor,and in the presence of an enzymatic catalyst capable of catalyzing theformation of ester bonds, and under reduced pressure sufficient tovaporize the solvent and by-product water, and continuously removing thewater.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph which illustrates the reduction of interfacial tensionbetween xylene and water afforded by biosurfactants prepared by aprocess according to the invention; and

FIG. 2 is a graph illustrating the stabilization of water/xyleneemulsions afforded by biosurfactants prepared by a process according tothe invention.

DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

Preferably, R contains from 4 to 24 carbon atoms, and X is a goodleaving group, R¹ can be derived from a carbohydrate (ose or oside) ofgeneral formula IIa or IIb or a polyol (especially a sugar alcohol or anoligoglycerol) of general formula III ##STR2## wherein R₁, R₂, R₃, R₄,and R₅ are the same or different, each being hydrogen, alkyl or arylgroup which can contain one or more hydroxy, carboxy, carbonyl, alkoxy,amino, amido, thio, bromo, fluoro, phosphate or sulfate groups.

Specific examples of carbohydrates include

fructose, where R₁ and R₄ =CH₂ OH, and R₂ and R₃ =H in formula IIa,

glucose, where R₁, R₂, R₃ and R₄ =H, and R₅ =CH₂ OH in formula IIb.

Examples of polyols can be

sorbitol, where R₁, R₂, R₃ and R₄ =H, and R₅ =H-(CHOH)₃ in formula III,

xylitol, where R₁, R₂, R₃ and R₄ =H, and R₅ =H-(CHOH)₂ in formula III,

glycerol, where R₁, R₂, R₃ R₄ and R₅ =H in formula III

Enzymes which may be useful as catalysts in the process of the inventionare those which catalyze the formation of ester linkages. Such enzymes,from animal, vegetable, microbial or fungal origin, include esterases,lipases, proteases or any other enzyme able to catalyze esterificationreactions. They may be in a soluble state, immobilized or encapsulated.They may be chemically or genetically modified in order to increasetheir activity in this kind of reaction.

The solvents which may be used for the process of the present inventionare those which are inert towards the reaction, do not inhibit thebiocatalyst and either forman azeotrope with water or have a boilingtemperature above 100° C. under atmospheric pressure. Examples of suchsuitable solvents are the tertiary alcohols (such asmethyl-2-butanol-2), the ketones (such as acetone, methyl-ethyl-ketone),the nitriles (such as acetonitrile) the alkanes (such as hexane,cyclohexane), just to mentioned a few. It will be appreciated by thoseskilled in the art that this list is by no means exhaustive.

The proposed process can be carried out in a conventional reactor. Thereactor includes a condensor and an external water-trap, for example, ofthe Soxhlet type, and is connected to a vacuum pump to reduce thepressure. The different reactants are placed in solution in the reactorwith the chosen solvent. After addition of the biocatalyst, the mixtureis allowed to reflux by lowering the pressure and increasingtemperature. The chosen pressure is such that the solvent and the waterproduced during the reaction pass progressively into the vapour phase.They recondense in the condenser and are led to the water-trap. Thewater held in the solvent is then trapped by molecular sieves locatedexternally of the reaction media in the water-trap. Thus, the solventwhich is continuously dried externally and returned to the reactionmedia, is anhydrous. At the end of the reaction, the biocatalyst isremoved (by filtration for example), the solvent dried under reducedpressure and the desired product recovered.

The water generated by the reaction is continuously removed as it isproduced without any solvent loss, which displaces the reactionequilibrium towards synthesis, and wherein the necessary activityrequired by the enzyme is maintained as there is no water accumulationin the media.

The present invention is further illustrated in the following examplesbut it should be understood that they do not in any way limit theinvention.

EXAMPLE 1 Preparation Of Sorbitol Monooleate

Oleic acid (0.156 g, 0.55 mmole) and sorbitol (1.010 g, 5.55 mmole) aredissolved in methyl-2-butanol-2 (100 ml). The soxhlet extractor containsmolecular sieves (3Å) and 50 ml of additional methyl-2-butanol-2. 1 g ofNovozym 435 (type B lipase of Candida antarctica manufactured by NovoInd.) is added and the reaction is performed under 100 mbar at 60° C. tohave the solvent refluxing. The progress of the reaction andquantification of each component are monitored by HPLC usinglaurophenone as an internal standard. At the end of the reaction, theenzyme is removed by filtration.

Oleic acid conversion is 98.5% in 24 hours. The yield in pure sorbitolmonooleate is equal to 95.6%.

EXAMPLE 2-16

In the following examples, the conditions in Example 1 have beenmodified to illustrate the large scale of application of the processdescribed in this invention. The following factors have been modified:

the molar ratio of hydroxyl donor/acyl donor,

the nature of the hydroxyl donor (sugar or sugar alcohol),

the nature of the acyl donor (fatty acid, fatty ester),

the biocatalyst,

the solvent.

Conditions used and obtained results are summarized in Table I.

In Table I, the numbers used have the following meanings:

1: +50 ml of the same solvent in the Soxhlet extractor cartridge.

2: acid conversion=(#mole acid at t₀ -#mole acid at t_(f))/#mole acid att₀, in %.

3: yield (mole %)

4: yield in triester (mole %)

5: yield of isolated monoester formed after purification on silicacolumn.

6: not detected under HPLC conditions used.

                                      TABLE 1                                     __________________________________________________________________________                                                   yield.sup.3 in                      hydroxyl    molar ratio             acid.sup.2                                                                          monoester                      example                                                                            donor acyl donor                                                                          OH/COOH                                                                              biocatalyst                                                                         solvent.sup.1                                                                      conditions                                                                          conversion                                                                          (diester)                      __________________________________________________________________________    1    sorbitol                                                                            oleic acid                                                                          10/1   Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 98.5% 95.6%                               1.010 g                                                                             0.156 g      435   methyl-2-                                                                          100 mbar     (2.8%)                             5.55 mmol                                                                           0.55 mmol    1 g   butanol-2                                                                          reflux                                     2    sorbitol                                                                            oleic acid                                                                          3/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 98.8% 91.0%                               1.010 g                                                                             0.522 g      435   methyl-2-                                                                          100 mbar     (7.7%)                             5.55 mmol                                                                           1.85 mmol    1 g   butanol-2                                                                          reflux                                     3    sorbitol                                                                            oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 97.9% 68.1%                               1.010 g                                                                             1.565 g      435   methyl-2-                                                                          100 mbar    (29.5%)                             5.55 mmol                                                                           5.55 mmol    1 g   butenol-2                                                                          reflux                                     4    sorbitol                                                                            oleic acid                                                                          1/3    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 67.5%  9.6%                               0.337 g                                                                             1.565 g      435   methyl-2-                                                                          100 mbar    (40.6%)                             1.85 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     5    glucose                                                                             oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 73.0% 73.0%                               1.000 g                                                                             1.565 g      435   methyl-2-                                                                          100 mbar      (0%)                              5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     6    fructose                                                                            oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 92.8% 65.1%                               1.000 g                                                                             1.565 g      435   methyl-2-                                                                          100 mbar    (26.2%)                             5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     7    xylitol                                                                             oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 98.0% 65.1%                               0.844 g                                                                             1.565 g      435   methyl-2-                                                                          100 mbar    (32.6%)                             5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     8    glycerol                                                                            oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 99.1% 66.6%                               0.511 g                                                                             1.565 g      435   methyl-2-                                                                          100 mbar    (30.6%)                             5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux      (1.5%.sup.4)                   9    sorbitol                                                                            caprylic                                                                            1/1    Novozym                                                                             100 ml                                                                              7 h, 60° C.                                                                 --    .sup.  42%.sup.5                    1.010 g                                                                             acid         435   methyl-2-                                                                          100 mbar                                        5.55 mmol                                                                           0.799 g      1 g   butanol-2                                                                          reflux                                                5.55 mmol                                                          10   sorbitol                                                                            lauric acid                                                                         3/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 98.5% 98.5%                               1.010 g                                                                             0.3705 g     435   methyl-2-                                                                          100 mbar    (nd.sup.6)                          5.55 mmol                                                                           1.85 mmol    1 g   butanol-2                                                                          reflux                                     11   sorbitol                                                                            erucic acid                                                                         3/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 99.2% 99.2%                               1.010 g                                                                             0.626 g      435   methyl-2-                                                                          100 mbar    (nd.sup.6)                          5.55 mmol                                                                           1.85 mmol    1 g   butanol-2                                                                          reflux                                     12   fructose                                                                            Me-oleate                                                                           1/1    Novozym                                                                             100 ml                                                                              7 h, 60° C.                                                                 60.1% 51.2%                                1.00 g                                                                             1.643 g      435   methyl-2-                                                                          100 mbar     (6.2%)                             5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     13   sorbitol                                                                            Me-oleate                                                                           1/1    Novozym                                                                             100 ml                                                                              7 h, 60° C.                                                                 47.6% 39.1%                               1.010 g                                                                             1.643 g      435   methyl-2-                                                                          100 mbar     (4.8%)                             5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     14   sorbitol                                                                            oleic acid                                                                          1/1    lipase                                                                              100 ml                                                                             24 h, 60° C.                                                                 94.9% 66.0%                               1.010 g                                                                             1.565 g      SP382 methyl-2-                                                                          100 mbar    (27.7%)                             5.55 mmol                                                                           5.55 mmol    1 g   butanol-2                                                                          reflux                                     15   sorbitol                                                                            oleic acid                                                                          1/1    Lipozyme                                                                            100 ml                                                                             24 h, 60° C.                                                                  2.6%  2.6%                               1.010 g                                                                             1.565 g      1 g   methyl-2-                                                                          100 mbar      (0%)                              5.55 mmol                                                                           5.55 mmol          butanol-2                                                                          reflux                                     16   glucose                                                                             oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 26.2% 26.2%                               1.000 g                                                                             1.565 g      435   ace- 300 mbar      (0%)                              5.55 mmol                                                                           5.55 mmol    1 g   tonitrile                                                                          reflux                                     17   glucose                                                                             oleic acid                                                                          1/1    Novozym                                                                             100 ml                                                                             24 h, 60° C.                                                                 27.2% 27.2%                               1.000 g                                                                             1.565 g      435   acetone                                                                            550 mbar      (0%)                              5.55 mmol                                                                           5.55 mmol    1 g        reflux                                     __________________________________________________________________________

EXAMPLE 17 Characterization of the Obtained Biosurfactants

The surfactant potential of the molecules prepared by the processdescribed in the present invention and purified on a silica column hasbeen evaluated by different means:

the measurement of the surface tension between water and air (Criticalmicelle concentration (CMC), efficiency and effectiveness of thesurfactants are presented in Table II),

the measurement of the interfacial tension between water and xylene(results are presented on FIG. 1),

the stabilization of water/xylene emulsions (the results of theexperiments carried out at 30° C. are presented in FIG. 2).Specifically, the solution of biosurfactant in water is mixed withxylene in a Polytron (trademark) mixer for 5 min. The emulsion formedwas transferred to a graduate cylinder placed at 30° C. and theseparation of phases is measured as a function of time.

                  TABLE II                                                        ______________________________________                                                                         EFFECTIVE-                                   PRODUCT   CMC        EFFICIENCY  NESS                                         ______________________________________                                        sorbitol mono-                                                                          1.2 * 10.sup.-2 M                                                                        4.3 * 10.sup.-4 M                                                                         26.3 dynes/cm                                caprylate                                                                     sorbitol mono-                                                                          2.5 * 10.sup.-4 M                                                                        2.1 * 10.sup.-5 M                                                                         29.4 dynes/cm                                laurate                                                                       sorbitol mono-                                                                          8.6 * 10.sup.-5 M                                                                        7.2 * 10.sup.-6 M                                                                         35.0 dynes/cm                                oleate                                                                        sorbitol mono-                                                                          7.4 * 10.sup.-5 M                                                                        1.4 * 10.sup.-5 M                                                                         39.0 dynes/cm                                erucate                                                                       fructose mono-                                                                          7.6 * 10.sup.-5 M                                                                        1.8 * 10.sup.-6 M                                                                         31.6 dynes/cm                                oleate                                                                        glucose mono-                                                                           8.9 * 10.sup.-5 M                                                                        3.4 * 10.sup.-6 M                                                                         33.2 dynes/cm                                oleate                                                                        xylitol mono-                                                                           3.5 * 10.sup.-5 M                                                                        2.1 * 10.sup.-6 M                                                                         29.7 dynes/cm                                oleate                                                                        ______________________________________                                         CMC: determined from the surface tension measurements (solution of            biosurfactant in water.                                                       EFFICIENCY: taken as the concentration of surfactant needed to reduce the     surface tension of water by 20 dynes/cm.                                      EFFECTIVENESS: minimum value to which the surfactant can lower the surfac     tension of water.                                                        

We claim:
 1. A process for the preparation of esters of general formulaI

    (R--COO--).sub.n --R.sup.1                                 (I)

wherein R is an alkyl group containing 4-24 carbon atoms which can besaturated or unsaturated, linear or branched and substituted orunsubstituted, n is 1 to 3 and R¹ is derived from a hydroxyl donorselected from a sugar and a polyol containing the moiety ##STR3## whichcomprises in a reactor, reacting a hydroxyl donor selected from a sugarand a polyol of formula

    R.sup.1 --(OH).sub.n

wherein R¹ and n are as defined above, with an acyl donor selected froma fatty acid and a fatty acid derivative of the formula

    R--CO--X

wherein R is as defined above and X is OH, OR', Cl or OOCR", in which R'and R" are an alkyl chain having 1-24 carbon atoms which can besaturated or unsaturated, linear or branched and substituted orunsubstituted, in a solvent therefor, wherein the solvent is inerttowards the reaction and does not inhibit the catalyst, selected fromthe group consisting of those which have a boiling point below 100° C.and form an azeotrope with water, and those which have a boiling pointabove 100° C. at atmospheric pressure, and in the presence of anenzymatic catalyst capable of catalyzing the formation of ester bonds,and under reduced pressure sufficient to vaporize the solvent andby-product water, and continuously removing the water while retainingthe solvent.
 2. A process according to claim 1, wherein water iscontinuously removed by condensing the solvent/water vapour and thenpassing through an external water trap to extract the water beforereturning the solvent to the reactor.
 3. A process according to claim 1,wherein the solvent is selected from the group consisting of tertiaryalcohols, ketones, nitriles and alkanes.
 4. A process according to claim3, wherein the catalyst is selected from the group consisting ofesterases, lipases and proteases.
 5. A process according to claim 1,wherein X is a good leaving group.
 6. A process according to claim 1,wherein R¹ contains the moiety of formula IIa ##STR4## wherein R₁, R₂,R₃, R₄ are the same or different, each being hydrogen, lower-alkyl whichcan contain one or more hydroxy, carboxy, carbonyl, alkoxy, amino,amido, thio, bromo, fluoro, phosphate or sulfate groups.
 7. A processaccording to claim 1, wherein R¹ contains the moiety of formula IIb##STR5## wherein R₁, R₂, R₃, R₄, and R₅ are the same or different, eachbeing hydrogen, lower-alkyl which can contain one or more hydroxy,carboxy, carbonyl, alkoxy, amino, amido, thio, bromo, fluoro, phosphateor sulfate groups.
 8. A process according to claim 1, wherein R¹contains the moiety of formula III ##STR6## wherein R₁, R₂, R₃, R₄, andR₅ are the same or different, each being hydrogen, lower-alkyl which cancontain one or more hydroxy, carboxy, carbonyl, alkoxy, amino, amido,thio, bromo, fluoro, phosphate or sulfate groups.
 9. A process accordingto claim 3, wherein the catalyst is a lipase.
 10. A process according toclaim 9, wherein the lipase is lipase B obtained from Candida antarcticaand the reaction temperature is 50°-70° C.
 11. A process according toclaim 6, wherein formula IIa, R₁ and R₄ =CH₂ OH and R₂ and R₃ =H.
 12. Aprocess according to claim 7, wherein formula IIb, R₁, R₂, R₃ and R₄ =Hand R₅ =CH₂ OH.
 13. A process according to claim 8, wherein formula III,R₁, R₂, R₃, and R₄ =H and R₅ =H(CHOH)₃.
 14. A process according to claim8, wherein formula III, R₁, R₂, R₃ and R₄ =H and R₅ =H(CHOH)₂.
 15. Aprocess according to claim 8, wherein formula III, R₁, R₂, R₃, R₄, andR₅ =H.
 16. A process according to claim 1, wherein the molar ratio ofhydroxyl donor: acyl donor is 1-10: 1-3.
 17. A process according toclaim 1, wherein the solvent is selected from the group consisting ofmethyl-2-butanol-2, acetonitrile and acetone.